CONFORMATIONAL STUDIES OF A SYNTHETIC CYCLIC DECAPEPTIDE FRAGMENT OF RAT TRANSFORMING GROWTH-FACTOR-ALPHA

The solution conformation of a synthetic cyclic decapeptide [with sequ ence mimicking the third disulfide loop of rat transforming growth fac tor-alpha (rTGF-alpha)] in deuterated dimethyl sulfoxide was studied b y 2D NMR. The determination of solution structures was based on NOE in terproton distances, using a combination of distance geometry and simu lated annealing protocols. The convergence of the selected structures was evident from the small atomic pairwise root-mean-square deviation values among them. Good agreement was noted between the experimental a nd simulated NOESY spectra, thereby reflecting the accuracy of the cal culated solution structures. Analysis of the structures indicates that the residues Tyr5 and Arg9 exhibit similar side chain orientation as that in the corresponding disulfide loop of human transforming growth factor-alpha. (C) Munksgaard 1995.